CHEMCATCHEM
FULL PAPERS
DOI: 10.1002/cctc.201200912
Synthesis of Chiral Ligands with Multiple Stereogenic
Centers and Their Application in Titanium(IV)-Catalyzed
Enantioselective Desymmetrization of meso-Epoxides
Manish Kumar, Rukhsana I. Kureshy,* Debashis Ghosh, Noor-ul H. Khan, Sayed H. R. Abdi,
and Hari C. Bajaj[a]
New chiral ligands, (S,R,S)-1, (S,S,S)-1, (S,S,R)-1, (S,R,R)-1, (R,R,R)-
1, (R,R,S)-1, (R,S,S)-1, (R,S,R)-1, (S,R,S)-2, (S,S)-3 and (R,S)-4 with
diverse stereogenic centers arising from various diastereomeric
combinations of aminoalcohol functionality with (R)- and (S)-
1,1-binaphthol, were prepared and characterized. Catalytically
active Ti complexes were generated in situ in the presence of
water for the enantioselective ring-opening reaction of meso-
stilbene oxide, cyclohexene oxide, cyclopentene oxide, and cis-
butene oxide with different anilines as nucleophile. Significant-
ly, catalysts Ti-(S,R,S)-1 and Ti-(R,S,S)-1 (15 mol%) produced syn-
beta-amino alcohols of meso-stilbene oxide with (1S,2S) and
(1R,2R) configuration respectively in excellent yields (>98%)
and enantioselectivities (ee value >99%) in 10 h at room tem-
perature. However, aliphatic/cyclic epoxides with aniline gave
better performance with the catalyst Ti-(S,R,R)-1. The complex
Ti-(S,R,S)-1 was successfully subjected to catalyst recovery and
recyclability experiments over 6 cycles in the asymmetric ring-
opening of meso-stilbene oxide with aniline with retention of
performance.
Introduction
The catalytic asymmetric ring-opening (ARO) reaction of an ep-
oxide with an amine is of prime interest as it allows the forma-
tion of chiral b-amino alcohol units, which are valuable build-
ing blocks for many biologically active compounds[1] and chiral
auxiliaries[2] in asymmetric synthesis. Various efficient catalytic
methods have been reported for the ARO of meso-epoxides
with alkyl/aryl amines using catalysts based on chiral ligands
with different metal ions viz., titanium,[3] niobium,[4] copper,[5]
lanthanides,[6] chromium,[7] iron,[8] scandium,[9] indium[10] and
bismuth[11] to provide b-amino alcohols in excellent yield and
enantioselectivity. Among these metal ions, titanium is of most
interest because of its non-toxic and environmentally benign
nature.[3] Furthermore, the design of chiral ligands has a direct
sway on the catalyst activity and enantioselectivity of the resul-
tant aminoalcohol and is a determining factor on the need of
additives, catalyst loading and the issue of separation and re-
cycling of the catalyst. Previous reports have described recycla-
ble chiral TiIV complexes based on chiral ligands (S)-1,1-binaph-
thol ((S)-BINOL),[3a] (1R,2S)-(ꢀ)-2-aminodiphenyl ethanol derived
Schiff bases[3b] and chiral polymeric salen[3c] for the ARO of
meso-epoxides in the presence of achiral/chiral additive. Prior
experience suggests that an additional element of chirality in
the catalytic concoction often improves the enantioselectivity
remarkably.[3b,c] This is in line with the reports on some other
reactions, for example, in carbon-carbon bond-forming reac-
tions in which introduction of new chiral centers (by use of
chiral additive) in the catalysts can lead to significant asymmet-
ric induction.[12] However, introduction of an additional chiral
center requires testing of all possible permutations and combi-
nations of individual chiral centers as matching and mismatch-
ing chirality has a pronounced effect on enantioselectivity (ee
value) and configuration of the product.[3b,c]
Based on this understanding in the present study the follow-
ing chiral ligands were designed: (S,R,S)-1, (S,S,S)-1, (S,S,R)-1,
(S,R,R)-1, (R,R,R)-1, (R,R,S)-1, (R,S,S)-1, (R,S,R)-1, (S,R,S)-2, (S,S)-3
and (R,S)-4. These have diverse stereogenic centers arising
from various diastereomeric combinations of aminoalcohol
functionality with (R)- and (S)-BINOL. An active catalyst was
generated in situ by using these chiral ligands with Ti(OiPr)4 to
catalyze ARO reaction of meso-stilbene oxide (5), cis-butene
oxide (7), cyclohexene oxide (8) and cyclopentene oxide
(9) with anilines 6a–f. We were pleased to find ligand (S,R,S)-1
(derived from (S)-5,5’-(1,1’-binaphthyl-2,2’-diylbis(oxy))bis(meth-
ylene)bis(3-tert-butyl-2-hydroxybenzaldehyde) with (1R,2S) cis-
1-amino-2-indanol) and (R,S,S)-1 (derived from (R)-5,5’-(1,1’-bi-
naphthyl-2,2’-diylbis(oxy))bis(methylene)bis(3-tert-butyl-2-hy-
droxybenzaldehyde) with (1S,2S) trans-1-amino-2-indanol)
works well in titanium catalyzed ARO of meso-stilbene oxide
(5) with aniline (6a), giving corresponding (1S,2S) and
(1R,2R) syn-b-amino alcohols, respectively, in excellent yield
(up to 98%) and enantioselectivity (ee value, >99%) in 10 h
[a] M. Kumar, Dr. R. I. Kureshy, D. Ghosh, Dr. N.-u. H. Khan, Dr. S. H. R. Abdi,
Dr. H. C. Bajaj
Discipline of Inorganic Materials and Catalysis
and
Academy of Scientific and Innovative Research
Central Salt and Marine Chemicals Research Institute (CSMCRI)
Council of Scientific & Industrial Research (CSIR)
G. B. Marg, Bhavnagar - 364 021, Gujarat (India)
Fax: (+91)0278-2566970
Supporting information for this article is available on the WWW under
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 2013, 5, 1 – 8 1
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